Reye's Syndrome (RS) is an often fatal, almost fulminating disease of children and adolescents with an unknown etiology and a high incidence in Michigan. The symptoms point strongly to a metabolic disturbance. To provide a better understanding of the metabolic disturbance as a basis for a rational approach to diagnosis, therapy and a laboratory means of monitoring it, an overview of the great variety of metabolic changes occurring in Reye's Syndrome will be obtained by examining the metabolic profile in tissues from Reye's Syndrome patients, in comparison with non-Reye's Syndrome patients as "controls". Similarly, tissues which seem to be primarily affected, as judged by their symptomatology, will be compared with other tissues (comparison or "control") which do not. The Lowry microchemical techniques will permit us to map all the intermediates of energy metabolism and thus identify cross-over points in different metabolic pathways of marked and therefore presumably key metabolic changes on which to focus in examining the primary as opposed to secondary metabolic alterations. In addition to these studies of the in vivo steady-state profile, the capacity of tissues to carry on specific dynamic processes will be examined in vitro, by testing the ability to utilize specific substrates. Similar studies carried on in the animal model will allow comparison to the patient samples and extension to tissues that are unavailable from patients. Furthermore, the possibility of a toxin in serum which might account for these metabolic disturbances will be investigated. Focusing on the site of the primary defect should enable us to better study the nature and origin of it and to design reasonable therapeutic steps to bypass the defect, i.e., to offset it by supplying an equivalent energy source.